rs768017195

Variant names:

• chr2-86858167-C-A
• rs768017195
• NM_004931.5:c.293G>T

Your query was ambiguous. Multiple possible variants found:

• chr2-86858167-C-A
• chr2-86858167-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_004931.5(CD8B):​c.293G>T​(p.Arg98Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000483 in 1,613,882 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R98Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000053 (1 hom.)
• Consequence: CD8B NM_004931.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.16
• Publications: 0 publications found

Genes affected

CD8B (HGNC:1707): (CD8 subunit beta) The CD8 antigen is a cell surface glycoprotein found on most cytotoxic T lymphocytes that mediates efficient cell-cell interactions within the immune system. The CD8 antigen, acting as a coreceptor, and the T-cell receptor on the T lymphocyte recognize antigens displayed by an antigen presenting cell (APC) in the context of class I MHC molecules. The functional coreceptor is either a homodimer composed of two alpha chains, or a heterodimer composed of one alpha and one beta chain. Both alpha and beta chains share significant homology to immunoglobulin variable light chains. This gene encodes the CD8 beta chain isoforms. Multiple alternatively spliced transcript variants encoding distinct membrane associated or secreted isoforms have been described. A pseudogene, also located on chromosome 2, has been identified. [provided by RefSeq, May 2010]

ENSG00000291013 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3219626).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004931.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD8B	NM_004931.5	MANE Select	c.293G>T	p.Arg98Leu	missense	Exon 2 of 6	NP_004922.1	P10966-1
	CD8B	NM_172213.5		c.293G>T	p.Arg98Leu	missense	Exon 2 of 6	NP_757362.1	P10966-6
	CD8B	NM_172101.5		c.293G>T	p.Arg98Leu	missense	Exon 2 of 7	NP_742099.1	P10966-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD8B	ENST00000390655.12	TSL:1 MANE Select	c.293G>T	p.Arg98Leu	missense	Exon 2 of 6	ENSP00000375070.6	P10966-1
	CD8B	ENST00000331469.6	TSL:1	c.293G>T	p.Arg98Leu	missense	Exon 2 of 6	ENSP00000331172.2	P10966-6
	CD8B	ENST00000393759.6	TSL:1	c.293G>T	p.Arg98Leu	missense	Exon 2 of 7	ENSP00000377356.2	P10966-2

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152212 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000239 AC: 6 AN: 251180 AF XY: 0.0000221

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000529

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000527 AC: 77 AN: 1461670 Hom.: 1 Cov.: 37 AF XY: 0.0000495 AC XY: 36 AN XY: 727146

African (AFR) AF: 0.0000299 AC: 1 AN: 33472

American (AMR) AF: 0.0000447 AC: 2 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.0000666 AC: 74 AN: 1111840

Other (OTH) AF: 0.00 AC: 0 AN: 60378

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152212 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 74354

African (AFR) AF: 0.00 AC: 0 AN: 41454

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68040

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.0000670 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.0000412 AC: 5

EpiCase AF: 0.000164

EpiControl AF: 0.000296

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	1.6
DANN	Benign	0.96
DEOGEN2	Benign	0.27	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0082	N
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.32	T
MetaSVM	Benign	-0.98	T
PhyloP100		-1.2
PrimateAI	Benign	0.19	T
PROVEAN	Uncertain	-4.3	D
REVEL	Benign	0.064
Sift	Benign	0.048	D
Sift4G	Benign	0.13	T
Polyphen		0.020	B
Vest4		0.24
MutPred		0.68		Loss of sheet (P = 0.1501)
MVP		0.39
MPC		0.70
ClinPred		0.092	T
GERP RS		-6.0
Varity_R		0.15
gMVP		0.62
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs768017195; hg19: chr2-87085290;